A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein.
A human lung cancer xenograft, LC-GP, producing granulocyte-colony stimulating factor and parathyroid hormone-related protein was established by transplantation into severe combined immunodeficient (SCID) mice. The lung cancer patient and SCID mice bearing LC-GP showed leukocytosis and hypercalcemia. G-CSF and PTHrP gene expression were demonstrated in the primary lung cancer, metastatic lesions and LC-GP xenograft. Immunohistochemical analysis confirmed the presence of G-CSF protein in LC-GP xenograft cells. LC-GP possessed activated c-Ki-ras oncogene (point mutation at codon 12). This LC-GP lacked apparent G-CSF receptor expression. The expression of G-CSF and PTHrP may be coregulated by the activated c-Ki-ras oncogene, and autocrine stimulation of G-CSF is unlikely.
Oshika
Y
Y
Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara-shi, Kanagawa 259-11, Japan.
Nakamura
M
M
Hatanaka
H
H
Abe
Y
Y
Tokunaga
T
T
Ohnishi
Y
Y
Kijima
H
H
Yamazaki
H
H
Tamaoki
N
N
Ueyama
Y
Y
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D015342:DNA Probes / Q000737:chemistry; D011905:Genes, ras / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D007964:Leukocytosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein; D017354:Point Mutation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D015342:DNA Probes; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor